JP5664967B2 - Aseptic connection device - Google Patents

Description

  The present invention relates to an aseptic connection device, and more particularly, a sealing means for forming a decontamination space for isolating a first lid and a second lid from an external atmosphere between a first sealed box and a second sealed box, and a supply pipe The present invention relates to an aseptic connection device comprising a decontamination medium supply means for supplying a decontamination medium vaporized through a passage to the decontamination space, and a discharge pipe for discharging the decontamination medium in the decontamination space.

Conventionally, an incubator is connected to an isolator, and the isolator and a transport container are communicated with each other while maintaining a sterilized state to transfer a culture or the like.
Here, when connecting the isolator and the transport container, in order to decontaminate these lids that have been exposed to the external atmosphere, the comparison between the isolator and the transport container is isolated from the external atmosphere. An aseptic connection device having a decontamination medium supply means for forming a decontamination space having a small capacity and supplying a decontamination medium vaporized via an air supply line to the decontamination space is known ( Patent Document 1).

JP 2010-195432 A

However, in the case of the configuration of Patent Document 1, since the decontamination space is formed in a state where the isolator and the transport container are separated, decontamination is performed by supplying a decontamination medium to the decontamination space in that state. After that, the isolator and the transport container are connected.
For this reason, although it is a small-capacity space, the decontamination space formed between the separated isolator and the transport container must be decontaminated, and the vaporized decontamination medium is sufficiently distributed, and It took time to remove the decontamination component by aeration.
In addition, there is a problem in that the use procedure is complicated because it is necessary to connect the isolator and the lid of the transport container after the decontamination space is decontaminated and to integrally open it.
In view of such a problem, the present invention provides a sterile connection device that makes a decontamination space a small-capacity space that surrounds a lid, and that can efficiently decontaminate the annular decontamination space. Is.

That is, according to the first aspect of the present invention, the first lid is provided between the first sealed box whose opening is closed by the first lid and the second sealed box whose opening is closed by the second lid. And a sealing means for forming a decontamination space for isolating the second lid from the external atmosphere, a decontamination medium supply means for supplying the decontamination medium vaporized to the decontamination space via a supply pipe line, In an aseptic connection device comprising a discharge conduit for discharging the decontamination medium in the decontamination space,
Providing a lid connecting means for connecting the first lid and the second lid to form the decontamination space in an annular decontamination space surrounding the lid;
In addition, a shielding member that prevents the flow of the decontamination medium is provided inside the annular decontamination space, and the annular decontamination space is partitioned into an elongated pipe-shaped decontamination space with the shielding member as an end. And
Further, the present invention is characterized in that a supply pipe line is connected to both end portions of the elongated decontamination space, and the discharge pipe line is connected between connection positions of the supply pipe lines.

According to the invention, since the decontamination space can be formed into an annular space surrounding the periphery of the lid by the lid connecting means, a space with a smaller capacity is formed as compared with the configuration of Patent Document 1. can do. Moreover, since the said 1st, 2nd cover body can be open | released immediately after completion | finish of decontamination, efficient decontamination work can be performed.
Further, the shielding member is provided inside the annular decontamination space to form an elongate pipe-shaped decontamination space, and supply pipes are connected to both ends of the elongate decontamination space, and between them. By connecting the discharge pipe, the decontamination medium can be quickly and uniformly distributed throughout the pipe-like decontamination space, and decontamination can be performed efficiently.

Configuration diagram of aseptic culture system according to the present embodiment Plan view showing the connection between the isolator and the incubator Side view showing the connection between the isolator and the incubator (A) is a separated state of the isolator and incubator, and (b) is a cross-sectional view showing these connected states. The figure explaining the shape of decontamination space The figure explaining the decontamination space of the shape different from the said Example

FIG. 1 shows an aseptic culture system 1 for culturing cells and tissues. FIG. 1 shows an isolator 2 as a first sealed box, an incubator 3 as a second sealed box, and the isolator 2 and the incubator 3. And an aseptic connection device 4 for communicating the internal space while maintaining a sterile condition.
The isolator 2 is provided with aseptic air supply means (not shown) for supplying aseptic air and decontamination means (not shown) for supplying a vaporized decontamination medium such as hydrogen peroxide water vapor. Before and after use, the interior space is decontaminated by a decontamination medium supplied by the decontamination means, and during use, the interior space is pressurized and maintained in an aseptic state.
Further, the isolator 2 has a glove 5 for an operator to perform aseptic operation and a pass box 6 for decontaminating and carrying in instruments and other samples used in the internal space of the isolator 2. Is provided.
A culture vessel is accommodated in the internal space 3A of the incubator 3, and the incubator 3 is movable while being placed on a carriage 3B.
The incubator 3 can be supplied with a gas suitable for culturing such as carbon dioxide from the outside, and the gas is blown out into the internal space 3A by a fan (not shown). The internal space 3A is kept at a predetermined temperature by a heater (not shown).
The isolator 2 and the incubator 3 are respectively provided with first and second openings 2b and 3b for communicating internal spaces with each other. As shown in FIG. 4, the first opening 2b of the isolator 2 is provided. Is closed by the first lid 11, and the second opening 3 b of the incubator 3 is closed by the second lid 21.
The aseptic connection device 4 includes a connecting means 7 for connecting the isolator 2 and the incubator 3, a lid connecting means 8 for connecting the first lid body 11 and the second lid body 21, the isolator 2 and the incubator 3. And a decontamination medium supply unit 10 for supplying a decontamination medium to the decontamination space S1.
According to the aseptic connection device 4, the isolator 2 and the incubator 3 that have been exposed to the outside until now are connected to the connection portion including the first and second openings 2 b and 3 b and the first and second lids 11 and 21. In addition to forming an annular decontamination space S1 with a small capacity, the internal space between the isolator 2 and the incubator 3 can be quickly communicated by decontaminating the decontamination space S1.

Hereinafter, the first and second lid bodies 11 and 21, the connection means 7, the lid connection means 8 and the sealing means 9 will be described with reference to FIGS. 4A shows a state where the isolator 2 and the incubator 3 are separated from each other, and FIG. 4B shows a state where the isolator 2 and the incubator 3 are connected by the connecting means 7.
A first opening 2b is formed in the side wall 2a of the isolator 2, and the internal space 2A of the isolator 2 is isolated from the external atmosphere by the first lid 11 provided in the first opening 2b so as to be opened and closed. ing.
The first opening 2b has a substantially rectangular shape with four corners being arcuate, and the cylindrical annular member 13 is kept airtight so as to protrude outward from the peripheral edge of the first opening 2b. It is fixed with.
A resin-made inner seal member 13a is provided at an end of the annular member 13 on the inner space 2A side of the isolator 2, and a resin-made outer seal member 13b is provided at an end of the outer atmosphere side.

As shown in FIG. 4, the first lid 11 is formed in a flat box shape having a rectangular opening 11a facing the outside of the isolator 2, and the outer periphery of the opening 11a A flat portion 11b that is in close contact with the inner seal member 13a of the annular member 13 is provided.
A resin-made first seal member 14 provided so as to surround the opening 11a is provided on the inner periphery of the contact surface of the flat portion 11b with the inner seal member 13a. The second lid 21 is in close contact with the second lid 21.
The first lid 11 is pivotally supported by a hinge 15 provided on the inner space 2A side of the isolator 2 so as to open to the inner space 2A side of the isolator 2, and an opening / closing lever 16 is also provided on the inner space 2A side. ing.
The opening / closing lever 16 can be operated from the inner space 2A side of the isolator 2 by an operator wearing the glove 5 of the isolator 2, and the fastener 17 provided with the opening / closing lever 16 on the inner surface of the side wall 2a. By engaging with the first lid 11, the first lid 11 is pressed against the inner seal member 13a, and the internal space 2A of the isolator 2 is sealed by the first lid 11.

A second opening 3b is formed in the side wall 3a of the incubator 3, and a second lid 21 is detachably provided in the second opening 3b by an attaching / detaching means 22. An internal space 3A of the incubator 3 is provided. Is isolated from the outside atmosphere.
The second opening 3b of the incubator 3 is formed in a substantially rectangular shape with four corners being arcuate, and a second seal member 23 is provided to project outside along the periphery of the second opening 3b. Yes.
The second lid body 21 is formed in a tray shape as shown in FIG. 4, and a bottom portion 21 a that is in close contact with the second seal member 23 provided in the second opening 3 b of the incubator 3, and a peripheral green portion of the bottom portion 21 a The peripheral wall 21b is erected from the peripheral wall 21b, and the peripheral surface 21c is formed by folding outward from the peripheral wall 21b.
As shown in FIG. 3, the attaching / detaching means 22 includes a total of four lock pins 24, which are provided so as to protrude from the top and bottom of the peripheral wall 21 b of the second lid 21, and the two pairs of lock pins 24. There are provided two connecting members 25 that are connected to each other, and four pin engaging members 26 that are provided on the side wall 3a of the incubator 3 and are respectively fitted to the four lock pins 24.
The lock pin 24 is slidably provided on the support member 27 fixed to the peripheral wall 21b of the second lid 21 in an airtight state. The lock pin 24 is slid from the inside of the peripheral wall 21b by a spring 28. It is urged to protrude outward.
With such a configuration, when the two connecting members 25 are separated by the urging force of the spring 28, the lock pin 24 engages with the pin engaging member 26, and the bottom portion of the second lid body 21. The state where 21a is in close contact with the second seal member 23 at the peripheral edge of the second opening 3b of the incubator 3 is maintained.
On the contrary, when the two connecting members 25 are brought close to each other against the biasing force of the spring 28, the lock pin 24 is detached from the pin engaging member 26, so that the second lid 21 is moved to the incubator 3. It is possible to make it more disengaged.

As shown in FIG. 2, the connecting means 7 is provided on the annular member 13 provided around the opening 11 a of the isolator 2 and on the side surface of the incubator 3 and engages with the hook 31. It is comprised from the ring 32, and these are each provided in the opposing position on both sides of the cyclic | annular member 13 and the incubator 3. As shown in FIG.
The isolator 2 and the incubator 3 can be connected and fixed so as not to be separated by engaging the ring 32 with the hook 31.

The lid connecting means 8 will be described. First, when the isolator 2 and the incubator 3 are coupled by the connecting means 7, the peripheral surface 21c of the second lid 21 is connected to the isolator 2 as shown in FIG. A lid inner space S2 that is in close contact with the first seal member 14 provided in the first lid 11 and is isolated from the external atmosphere is formed inside the first lid 11 and the second lid 21. ing.
The lid connecting means 8 includes two air cylinders 33 on the inner side of the opening 11a in the first lid 11, and a conical concave insertion hole is formed at the top of the piston rod of the air cylinder 33 in the vertical direction. A total of four abutting portions 33a facing each other are provided so as to move up and down.
An air pipe 33b is connected to the air cylinder 33 with the internal space 2A of the isolator 2 kept airtight, and air is supplied from an air supply source (not shown) through the air pipe 33b. .
On the other hand, the two connecting members 25 in the second lid body 21 are each provided with two engaging pins 34 between the two lock pins 24 as shown in FIG. When the abutting portion 33a is moved forward and backward by 33, the abutting portion 33a is fitted to each engaging pin 34, respectively.

According to the lid connecting means 8 having the above configuration, when the isolator 2 and the incubator 3 are connected and fixed by the connecting means 7 and the first lid 11 and the second lid 21 are in close contact with each other, the air cylinder 33 is used. Brings the abutment portions 33a closer to each other.
Then, the contact portion 33a is engaged with an engagement pin 34 provided on the second lid body 21, and then the air cylinder 33 presses the engagement pin 34 to attach the connecting member 25 to the spring 28. When approaching each other against the force, the lock pin 24 is detached from the pin engaging member 26 provided around the opening 11 a of the incubator 3.
As a result, the first lid 11 and the second lid 21 are connected to form the lid internal space S2, and the second lid 21 can be detached from the incubator 3, so that the first lid The body 11 and the second lid body 21 can be opened and closed toward the internal space 2A of the isolator 2 in a state where the body 11 and the second lid body 21 are integrally connected.

The sealing means 9 includes the annular member 13 that endlessly surrounds the first opening 2b of the isolator 2, and a projecting member 35 that endlessly surrounds the second opening 3b of the incubator 3. Yes.
The outer seal member 13b is provided on the surface of the annular member 13 facing the incubator 3, and the protruding member 35 is further provided on the periphery of the second opening 3b. It is provided so as to surround the outside.
With such a configuration, when the isolator 2 and the incubator 3 are connected by the connecting means 7, the outer seal member 13b and the projecting member 35 are in close contact with each other as shown in FIG. A more decontaminated space S1 having a volume of about 20 to 40 l is formed.
Moreover, the decontamination space S1 isolated by the sealing means 9 forms an annular space surrounding the first and second lid bodies 11 and 21 connected by the lid connecting means 8. The decontamination space S1 and the lid internal space S2 do not communicate with each other.
The sealing means 9 may be provided in either the isolator 2 or the incubator 3. For example, the outer sealing member 13b can be omitted by using the projecting member 35 as a sealing member that is in close contact with the wall surface around the first opening 2b of the isolator 2.

A shielding member 36 that prevents the flow of the decontamination medium is provided inside the annular decontamination space S1 in the present embodiment, and the annular decontamination space S1 is formed into an elongated pipe-shaped decontamination space S1. It comes to divide into.
As shown in FIG. 3, the shielding member 36 is provided in the upper center of the annular decontamination space S <b> 1, and as shown in FIG. 4A, the shielding member 36 is attached to the annular member 13 of the isolator 2. Consists of three plate-like members consisting of a fixed member 36a, a member 36b provided on the protruding member 35 of the incubator 3, and a member 36c provided on the outer peripheral side of the peripheral wall 21b of the second lid 21. Has been.
Then, as shown in FIG. 4B, when the isolator 2 and the incubator 3 are connected and the first and second lids 11 and 21 are connected, these members 36a to 36c are combined, and the decontamination is performed. The space S1 is partitioned.
The shielding member 36 does not need to completely block the decontamination space S1 when the members 36a to 36c are combined, and the member 36a can be used as long as the flow of the decontamination medium in the decontamination space S1 can be prevented. A slight gap may be formed between ˜36c.

The decontamination medium supply means 10 supplies hydrogen peroxide vaporized by evaporating an aqueous hydrogen peroxide solution as a decontamination medium, and the decontamination medium includes the decontamination medium supply means 10 and a sealing means. 9 is supplied to the decontamination space S <b> 1 through a supply pipe 41 disposed between the two.
An HEPA filter 42 is provided in the middle of the supply pipe 41, and the supply pipe 41 is branched into supply pipes 41 a and 41 b at positions adjacent to the HEPA filter 42 to form the sealing member 9. 13 and connected to a position sandwiching the shielding member 36.
In other words, the decontamination space S1 is partitioned into an elongated pipe-shaped space by the shielding member 36, but the supply conduits 41a and 41b are the end of the decontamination space S1. By being connected to a position close to one surface and the other surface, the decontamination medium is supplied from both end portions of the elongated pipe-shaped decontamination space S1.
A discharge pipe 43 for discharging the gas inside the decontamination space S1 is connected to the lower part of the annular member 13 constituting the sealing means 9, and the discharge pipe 43 is a slender pipe-like decontamination space. In S1, it connects between the connection position of the supply pipe line 41a used as the edge part, and the connection position of the supply pipe line 41b. The exhaust pipe 43 is provided with a HEPA filter 44 and a catalyst 45 for decomposing the decontamination medium.

Hereinafter, a method for using the aseptic connection device 4 according to the present invention will be described, and in particular, a procedure for decontamination of the decontamination space S1 from a state where the isolator 2 and the incubator 3 are connected by the connection means 7 will be described.
First, when the isolator 2 and the incubator 3 are connected by the connecting means 7 and the first and second lid bodies 11 and 21 are connected by the lid connecting means 8, the decontamination space S1 is formed by the sealing means 9. In addition, the decontamination space S1 is formed in an annular space surrounding the first and second lid bodies 11 and 21.
As a result, the decontamination space S1 is partitioned from the external atmosphere and the lid body internal space S2. However, the decontamination space S1 includes a portion that has been exposed to the external atmosphere until then. If the first and second lids 11 and 21 are opened as they are, the internal spaces 2A and 3A of the isolator 2 and the incubator 3 may be contaminated by bacteria attached to the exposed portions.
Therefore, in this embodiment, the decontamination space S1 is decontaminated so that the first and second lids 11 and 21 can be opened in a sterile state, and the internal spaces 2A and 3A are communicated with each other in a sterile state. Thus, the culture can be transferred between the incubator 3 and the isolator 2.

As described above, by connecting the isolator 2 and the incubator 3 and connecting the first and second lids 11 and 21, as shown in FIG. An annular decontamination space S <b> 1 is formed, and the decontamination space S <b> 1 is formed into an elongated pipe-like space by the shielding member 36.
The supply pipes 41a and 41b are connected to both ends of the slender pipe-shaped decontamination space S1, that is, on the one side and the other side of the shielding member 36, and the supply pipes 41a and 41b are further connected. The discharge pipe 43 is connected between the pipes 41a and 41b. In this embodiment, it is connected to the middle part of the pipe-shaped decontamination space S1.
With this configuration, when the decontamination medium vaporized by the decontamination medium supply means 10 is supplied to the supply pipeline 41, the decontamination medium is disposed at both ends of the elongated decontamination space S1. It will flow from the part.
Thereafter, the decontamination medium flows in one direction toward the discharge pipe 43, joins at a position where the discharge pipe 43 is connected, and is discharged from the discharge pipe 43, thereby removing the air in the decontamination space S1. Replace with vaporized decontamination media. In addition, since each supply pipeline 41a, 41b is made to approach the shielding member 36, the decontamination medium flows also to the shielding member 36 side, is folded by the shielding member 36, and flows to the discharge pipeline 43 side.
In this way, by dividing the annular decontamination space S1 into a long and narrow duct-like space by the shielding member 36, the decontamination medium that has flowed into the decontamination space S1 can be filled quickly and uniformly.

When the decontamination medium is thus filled in the decontamination space S1, the electromagnetic valve is closed to stop the inflow and discharge of the gas, and the vaporized decontamination medium is held in the decontamination space S1. For example, by keeping this state for 3 minutes, the vaporized decontamination medium is made into droplets and adheres to the member exposed to the inside of the decontamination space S1.
When the decontamination medium is held for a predetermined time, the decontamination medium supply means 10 supplies air that does not include the decontamination medium, and performs aeration for discharging the decontamination medium from the decontamination space S1 for a predetermined time.
When these operations are completed, the operator wears the glove 5 provided in the isolator 2 and operates the open / close lever 16 from the inside of the isolator 2 to integrally couple the first lid 11. And the 2nd cover body 21 is opened toward the inside of the isolator 2, and the internal space 2A of the isolator 2 and the internal space 3A of the incubator 3 are mutually communicated.
At this time, the portion exposed to the decontamination space S1 is decontaminated, and the lid internal space S2 of the first and second lids 21 is sealed by the lid connecting means 8, The portions exposed to the external atmosphere are not exposed to the internal spaces 2A and 3A of the isolator 2 and the incubator 3 without being decontaminated.
Further, when the work in the incubator 3 and the isolator 2 is finished and the connection is released, the operator first operates the opening / closing lever 16 so that the first lid body 11 and the second lid body 21 are integrated. The connection state of the first and second lid bodies 11 and 12 by the lid body connecting means 8 is released, and the connection state of the incubator 3 and the isolator 2 by the connecting means 7 is released.
When there is a possibility that cells and tissues handled in the internal space 2A of the isolator 2 are contaminated with harmful substances such as microorganisms, bacteria, and viruses, the decontamination space S1 is formed by the sealing means 9. Therefore, it is possible to decontaminate the decontamination space S1 again using the decontamination medium supply means 10.
Then, the operator can move the incubator 3 to an arbitrary place and connect another incubator 3 to the isolator 2.

As described above, according to the aseptic connection device 4 having the above-described configuration, the isolator 2 and the incubator 3 are connected by the connecting means 7, and the first lid body 11 and the second lid body 21 are surrounded by an annular shape. Since the decontamination space S1 is formed, the small-volume decontamination space S1 can be quickly decontaminated, and the isolator 2 and the incubator 3 can be efficiently communicated with each other.
In addition, by providing the shielding member 36 inside the annular decontamination space S1, the decontamination space S1 is formed into an elongated pipe-shaped space, and the supply pipe line is located close to the shielding member 36. 41a and 41b are connected and a decontamination medium is supplied from the one end part and other end part of elongate pipe-shaped decontamination space S1.
As a result, the decontamination medium flows in one direction toward the discharge pipe 43 without turbulent diffusion along the inside of the decontamination space S1, and quickly and uniformly with respect to the entire inside of the decontamination space S1. Can be spread over decontamination media.
On the other hand, when the decontamination medium is discharged from the discharge pipe 43, the decontamination medium joins in the vicinity of the discharge pipe 43 to generate a turbulent flow, so that it faces the position where the discharge pipe 43 is connected. The decontamination medium can be spread over the outer peripheral surfaces of the first and second lid bodies 11 and 21.
On the other hand, when the decontamination medium is introduced from one supply pipe 41 into the annular decontamination space S1 without providing the shielding member 36, the inflowing decontamination medium is the annular decontamination medium. There is a risk that the decontamination effect may vary because the decontamination medium may not be evenly distributed after flowing into the space S1 and the decontamination medium may not be distributed uniformly.
In addition, although the shielding member 36 is provided to form a slender pipe-like decontamination space S1, a supply pipe 41 is provided at one end of the pipe-like decontamination space S1, and a discharge pipe 43 is provided at the other end. In this configuration, the decontamination medium flows in one direction, but the decontamination medium is immediately discharged from the discharge pipe 43 at the portion where the discharge pipe 43 is connected. There arises a problem that the decontamination medium does not sufficiently spread to the corners of the shield member 36 at the part.

In contrast to the configuration in which one shielding member 36 is provided for the decontamination section shown in FIG. 5, two or more shielding members 36 are provided as shown in FIG. The dyeing space S1 may be formed.
As shown in FIG. 6, when two shielding members 36 are provided at positions facing each other with the first and second lid bodies 11 and 21 therebetween, the decontamination space S1 is formed in a substantially U-shaped elongated pipe line by the shielding members 36. Two shaped spaces are formed vertically.
In this case, different shielding members 36 are located at the end portions of the pipe-shaped decontamination space S1, and the supply conduits 41 are connected in the vicinity of the shielding members 36, and are connected to one end and the other end. The discharge pipeline 43 is connected between the connection positions of the supply pipelines 41.

DESCRIPTION OF SYMBOLS 1 Aseptic culture system 2 Isolator 3 Incubator 4 Aseptic connection apparatus 7 Connection means 8 Cover body connection means 9 Sealing means 10 Decontamination medium supply means 11 First lid body 21 Second lid body 36 Shielding member 41 Supply line 42 Discharge line S1 decontamination space

Claims (2)

Between the first sealed box whose opening is closed by the first lid and the second sealed box whose opening is closed by the second lid, the first lid and the second lid are placed in an external atmosphere. Sealing means for forming a decontamination space to be isolated from the decontamination medium, a decontamination medium supply means for supplying the vaporized decontamination medium to the decontamination space through a supply pipe, and a decontamination medium in the decontamination space In a sterile connection device comprising a discharge conduit for discharging
Providing a lid connecting means for connecting the first lid and the second lid to form the decontamination space in an annular decontamination space surrounding the lid;
In addition, a shielding member that prevents the flow of the decontamination medium is provided inside the annular decontamination space, and the annular decontamination space is partitioned into an elongated pipe-shaped decontamination space with the shielding member as an end. And
Furthermore, the aseptic connection device is characterized in that a supply pipe line is connected to each of both end portions of the elongated decontamination space, and the discharge pipe line is connected between connection positions of the supply pipe lines.   The aseptic connection apparatus according to claim 1, wherein two or more shielding members are provided, and the decontamination space is divided into two or more by the shielding members.

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